This is a competing continuation application for the Community Vulnerability and Responses to Drug-User- Related HIV/AIDS study of why large US metropolitan areas vary over time in their vulnerability to HIV/AIDS among drug users and in their responses-i.e., in policies and programs that may affect the epidemic. Drug use and HIV epidemics change over time. In the last funding period, we showed that HIV prevalence in the 96 largest US metropolitan areas declined among injection drug users (IDUs) from 1992 to 2002, and that the population prevalence of IDUs declined in these areas from 1992 to 2000, but then began to rise again. We also showed that metropolitan areas varied in these trajectories, and that a variety of social and policy forces shaped IDU prevalence, racial disparities in IDU prevalence, HIV prevalence among IDUs, racial disparities in AIDS prevalence among IDUs, drug abuse treatment coverage, and syringe exchange access and coverage. Ominously, our recent analyses indicate that the prevalence of IDUs among youth (aged 15 - 29) has begun to rise. Further, as others have shown, HIV has spread widely among NIDUs (non-injecting users of heroin, cocaine, crack, amphetamines or methamphetamine) in some metropolitan areas. These changes are occurring against the backdrop of an economy that has recently shifted from slow to rapid decline, a shift that will lead to great difficulty in maintaining, let alone expanding, services for drug users. Therefore, the Specific Aims of this proposed continuation are: 1. To describe trends, in the 96 largest US metropolitan areas from 1992 - 2012, in (a) critical epidemiologic outcomes (population prevalence of IDUs and NIDUs, and particularly their prevalence among youth; and, among IDUs, HIV prevalence, late-diagnosis HIV cases, and AIDS incidence and mortality) as well as in (b) the implementation of evidence-based drug- related interventions (drug abuse treatment, syringe exchange, HIV counseling and testing) and (c) non- evidence-based drug-related interventions (incarceration and arrests of drug users). 2. To understand how macro-social contexts (e.g., economic changes, social integration, racial residential segregation) and epidemiologic need affect interventions; how interventions and macro-social contexts together affect epidemiologic contexts; how some interventions (e.g., arrests, incarceration) affect others (e.g., syringe exchange coverage); and how some epidemiologic outcomes (e.g., prevalence of young IDUs) affect others (e.g., HIV prevalence). 3. To develop an integrated theory, using agent based modeling, of how these processes interact and thus what the impacts of various intervention mixes are likely to be in given social contexts. 4. To disseminate estimates, results and theoretical understandings to public health agencies and continue to advise them on how they might respond.